X-43728763-C-T

Variant names:

• chrX-43728763-C-T
• rs6610845
• NM_000240.4:c.645+449C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000240.4(MAOA):​c.645+449C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.506 in 111,701 control chromosomes in the GnomAD database, including 11,627 homozygotes. There are 16,944 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.51 (11627 hom., 16944 hem., cov: 24)
• Consequence: MAOA NM_000240.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.453
• Publications: 5 publications found

Genes affected

MAOA (HGNC:6833): (monoamine oxidase A) This gene is one of two neighboring gene family members that encode mitochondrial enzymes which catalyze the oxidative deamination of amines, such as dopamine, norepinephrine, and serotonin. Mutation of this gene results in Brunner syndrome. This gene has also been associated with a variety of other psychiatric disorders, including antisocial behavior. Alternatively spliced transcript variants encoding multiple isoforms have been observed. [provided by RefSeq, Jul 2012]

MAOA Gene-Disease associations (from GenCC):

• Brunner syndrome

  Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, ClinGen, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.653 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000240.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAOA	NM_000240.4	MANE Select	c.645+449C>T		intron	N/A	NP_000231.1	Q53YE7
	MAOA	NM_001270458.2		c.246+449C>T		intron	N/A	NP_001257387.1	P21397-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAOA	ENST00000338702.4	TSL:1 MANE Select	c.645+449C>T		intron	N/A	ENSP00000340684.3	P21397-1
	MAOA	ENST00000967111.1		c.645+449C>T		intron	N/A	ENSP00000637170.1
	MAOA	ENST00000873971.1		c.645+449C>T		intron	N/A	ENSP00000544030.1

Frequencies

GnomAD3 genomes AF: 0.506 AC: 56493 AN: 111643 Hom.: 11638 Cov.: 24

Gnomad AFR AF: 0.200

Gnomad AMI AF: 0.553

Gnomad AMR AF: 0.611

Gnomad ASJ AF: 0.627

Gnomad EAS AF: 0.421

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.594

Gnomad MID AF: 0.624

Gnomad NFE AF: 0.659

Gnomad OTH AF: 0.528

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.506 AC: 56479 AN: 111701 Hom.: 11627 Cov.: 24 AF XY: 0.499 AC XY: 16944 AN XY: 33925

African (AFR) AF: 0.200 AC: 6182 AN: 30895

American (AMR) AF: 0.610 AC: 6425 AN: 10534

Ashkenazi Jewish (ASJ) AF: 0.627 AC: 1656 AN: 2642

East Asian (EAS) AF: 0.421 AC: 1482 AN: 3518

South Asian (SAS) AF: 0.358 AC: 986 AN: 2758

European-Finnish (FIN) AF: 0.594 AC: 3516 AN: 5916

Middle Eastern (MID) AF: 0.627 AC: 136 AN: 217

European-Non Finnish (NFE) AF: 0.659 AC: 34914 AN: 53009

Other (OTH) AF: 0.526 AC: 809 AN: 1538

Alfa AF: 0.612 Hom.: 42643

Bravo AF: 0.495

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.85
DANN	Benign	0.68
PhyloP100		-0.45
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs6610845;

hg19: chrX-43588010;

COSMIC: COSV58643172;